Date of Award
MD (Medical Doctor)
Professor M Cafferkey
Professor K Butler
Newborn, Screening, Congenital, Toxoplasmosis, Ireland
Introduction: The majority of infants with congenital toxoplasmosis (CT) in Europe are asymptomatic and remain undetected during routine postnatal care. Postnatal screening for CT facilitates early diagnosis, targeted therapy and intervention to optimise neurodevelopmental outcome. A previous study in Ireland demonstrated that maternal toxoplasma seroprevalence was 25%, which implied that 75% remained susceptible to seroconversion in pregnancy. Thus funding was sought for a study to determine 1) the feasibility of postnatal screening for CT, 2) the incidence of CT and 3) outcome during the first decade of life.
Methods: A two-year pilot newborn screening programme was initiated on July 1st 2005. A two-step IgM screening protocol was employed (AutoDELFIA and ISAGA assays) to test dried heel blood spots obtained 72-120 hours after birth. Diagnosis was confirmed using paired mother/infant serology. Detailed clinical evaluation, one-year anti-protozoal therapy and clinical follow-up was offered to all diagnosed infants.
Results: Toxoplasma IgM was easily recovered from dried heel blood. The screening assays were not highly predictive. Thirty-four screened positive, 19 were false positives. A diversity of confirmatory serology was encountered that necessitated serial testing in a minority. Congenital toxoplasmosis was confirmed in 15 children giving an incidence of 1 per 10,000 births. Two of 15 (13%) were symptomatic. Thirteen of 15 (87%) were asymptomatic, four (31%) of whom had detectable clinical signs: all four had inactive chorioretinal scars and two had intracranial calcification. Most women seroconverted in trimester 3 and reported food sources as risk factors with lack of awareness. Antiprotozoal treatment was prescribed for 14 infants; reversible neutropenia was common during treatment. One asymptomatic child was not treated due to non-confirmatory serology up to nine months. Median follow-up was 9 years (range 2 to 10 years). Fourteen have normal neurodevelopmental outcome and visual acuity including one asymptomatic infant who had a unilateral inactive retinal lesion at birth that reactivated at age two years. Regression of intracranial calcification and ventriculomegaly was noted following treatment completion. One child with hydrocephalus and ventriculoperitoneal shunt has minor co-ordination deficits but normal cognition and attends main stream school.
Discussion: The low incidence of CT in Ireland was comparable with rates previously reported for other parts of Western Europe. The rate of false positive screening results (1.3 per 10,000) demonstrates that if CT were to be considered for inclusion in the routine postnatal screening programme, alternative screening assays would be more desirable than those chosen for this study. The predominance of asymptomatic cases of CT was likely due to the avirulent type II strain of T. gondii in Europe plus predominance of trimester 3 seroconversion in the cohort of women with infected infants. However, lesions in the central nervous system were detected only because of screening in one third of asymptomatic infants. The maternal dietary and lifestyle risk factors identified in the study can be potentially targeted as future primary prevention strategies for CT in Ireland. The frequency of adverse events encountered during antiprotozoal treatment demonstrated the need for alternative, less toxic treatment regimens for CT and research in this area. Reactivation in an asymptomatic child with subclinical disease on evaluation demonstrates the importance of treatment and ophthalmological surveillance for all cases of CT and not just those with symptoms or severe signs at initial assessment. Overall, better than anticipated visual and neurodevelopmental outcomes were demonstrated in children with CT where early treatment was facilitated by the postnatal screening program. Limitations to this study were the small sample size of 15 infected infants and lack of an untreated control group.
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Ferguson W. Newborn screening for congenital toxoplasmosis in Ireland [MD Thesis]. Dublin: Royal College of Surgeons in Ireland; 2016.